Vinyl azides in heterocyclic synthesis. Part 10. Synthesis of the isoindolobenzazepine alkaloid lennoxamine

Abstract

A total synthesis of the isoindolobenzazepine alkaloid lennoxamine (1), by a route involving vinyl azide chemistry, is described. Model studies on the azidocinnamates (12) and (13) revealed a striking difference between the (E)-and (Z)-isomers; whereas the (Z)-isomer (12) and gave largely the 1-benzylisoquinoline (15) on decomposition, the (E)-isomer (13) gave the 2-aryl-3-benzazepine (14) as the major product. Consequently, in the lennoxamine synthesis, the azidocinnamate (26) bearing the (E)-alkenyl side chain, prepared from 6-bromopiperonal via the (E)-stilbene aldehyde (25)(Scheme 4), was decomposed to give the key 2-aryl-3-benzazepine (27). Reduction of the double bonds in (27) was accompanied by cyclisation to the tetrahydroisoindolo[1,2-b][3]benzazepine (30), which was converted into lennoxamine (1) by reduction of the ester group to an aldehyde, and decarbonylation.